Differential effects of two doses of aspirin on platelets-vessel wall introduction in vivo.
Platelet cyclooxygenase appears to be more sensitive to aspirin than the arterial endothelial cell cyclooxygenase. To investigate the dose-related effects of aspirin on platelet-vessel wall interaction in acute vascular injury, male New Zealand White rabbits were treated with either (a) aspirin (150 mg/kg body wt; n = 6), (b) aspirin (30 mg/kg; n = 6), or (c) vehicle (n = 10). After treatment, autologous 111In-platelets were injected and deendothelialization of a 10-cm long segment of abdominal aorta was induced by a balloon catheter. Rabbits were killed 3 h after injury and radioactive counts and percentages of injected radioactivity per gram dry weight of tissue or blood were determined. The 30 mg aspirin group had a significantly lower radioactive count (62.13 +/- SD 6.07 x 10(3) cpm) and percentage of injected radioactivity (0.024 +/- 0.003%) per gram dry weight of damaged aortic tissue than the control (1,167.82 +/- 212.31 x 10(3) cpm/g tissue and 0.435 +/- 0.079%, respectively). By contrast, the 150-mg aspirin group had an elevation of radioactive counts (4,343.12 +/- 556.98 cpm) and percentage (1.632 +/- 0.246%) per gram dry weight of damaged tissue. Infusion of exogenous PGI2 was associated with reduction of lesion radioactivity. These findings were supported by ultrastructural findings. Examined under transmission electron microscopy, the injured aortic wall of 30-mg group was covered throughout the segment by a single layer of platelets without detectable platelet aggregates, while that of the 150-mg group was diffusely packed with multiple layers of platelets. The findings demonstrate that aspirin (30 mg/kg) prevents platelet aggregate formation at the injured arterial wall, whereas 150 mg/kg promotes platelet thrombus formation.
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000293:injuries; D001241:Aspirin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000201:enzymology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits
D016861:Cyclooxygenase Inhibitors; D001241:Aspirin